Therapeutic prospects for epigenetic modulation

Epigenetics describes the phenomenon of heritable changes in gene regulation governed by non-Mendelian processes, primarily through biochemical modifications to chromatin that occur during cell differentiation and development. Abnormal levels of DNA and/or histone modifications are observed in patients with a wide variety of chronic diseases. Drugs that target the proteins controlling these chromatin modifications can modulate the expression of clusters of genes, potentially offering higher therapeutic efficacy than classical agents with single target pharmacologies that are susceptible to biochemical pathway degeneracy.

This article reviews research characterizing dysregulation of epigenetic processes in cancer, immuno-inflammatory, psychiatric, neurological, metabolic and virology disease areas, and summarizes recent developments in identifying small molecule modulators that are being used to inform target discovery and initiate drug discovery projects.

There are numerous potential opportunities for epigenetic modulators in treating a wide range of chronic diseases; however, the field is complex, involving > 300 proteins, and much work is still required to provide tools to unravel the functions of individual proteins, particularly in vivo. This groundwork is essential to allow the drug discovery community to focus on those epigenetic proteins most likely to be suitable targets for safe, efficacious new therapies.